Administering Nusinersen

Nusinersen (Spinraza) is the first FDA-approved antisense oligonucleotide indicated for the treatment of spinal muscular atrophy (SMA) in adults and children.1,2 The oligonucleotide is administered intrathecally2; thus, administration is not as straightforward as an intravenous infusion. As such, healthcare professionals should understand how to administer nusinersen before attempting to do so. Ideally, healthcare professionals who administer nusinersen will be competent in performing lumbar puncture, lumbar puncture offers a route for intrathecal administration.3

Dosing and timing considerations

Nusinersen (Spinraza) is a clear, colorless solution supplied in a single-dose glass vial. Each vial contains 12 mg of the oligonucleotide dissolved in 5 mL of sterile, preservative-free solution. Every loading and maintenance dose is 12 mg, thus the entire 5 mL volume contained in the vial is administered during infusion.2 

Per the manufacturer, nusinersen (Spinraza) should be stored in a refrigerator (2°C-8°C; 36°F-46°F) in its original carton until immediately prior to use. It should never be frozen. If refrigeration is not possible, the product is stable and usable for up to 14 days if kept at or below 30°C (86°F), protected from light, and in its original carton. Once removed from its carton, the oligonucleotide is stable for a maximum of 30 hours if kept during that entire time at an ambient temperature 25°C (77°F) or below.2 Nusinersen should be administered within four hours of removing the product from its single-dose glass vial. The product should be allowed to warm to room temperature before administration, assuming room temperature is not in excess of 25°C (77°F).2

Nusinersen is administered in a set of four loading doses followed by maintenance dosing. The first, second, and third doses of nusinersen are separated in time by 14 days. The fourth dose is administered 30 days after the third dose. Once the fourth and final loading dose has been administered, the patient should receive maintenance doses every four months. If the patient misses any loading or maintenance dose, it should be administered as soon as practically possible. On the other hand, no two doses of nusinersen should be given within 14 days of one another.2

Requisite testing

The prescribing instructions recommend that practitioners obtain a platelet count, coagulation laboratory testing, and quantitative spot urine protein testing. at baseline and prior to each dose. The use of some antisense oligonucleotides is associated with severe acute thrombocytopenia.4 In one clinical trial, the rate of thrombocytopenia in patients taking nusinersen was 16% (24 of 146 patients) compared to 14% (10 of 72 patients) receiving sham control.2 

Seventy-one of 123 patients (58%) receiving nusinersen developed proteinuria, while only 22 of 65 patients (34%) undergoing the sham procedure developed elevated urine protein.2  The quantitative spot urine protein test is used for this reason and since renal toxicity (e.g. glomerulonephritis) is a possible adverse effect of antisense oligonucleotides; the manufacturer recommends obtaining a quantitative spot urine protein test at baseline and prior to each dose. Ideally, the sample is collected from the first urination after waking in the morning. A urinary protein concentration greater than 0.2 g/L could be considered a relative contraindication to nusinersen (Spinraza) until the issue is worked up and resolved.2

Patient positioning and administration

The patient may be positioned in the lateral decubitus, lateral recumbent, prone, or seated positions. Patient positioning is important as it can maximize the space between vertebral bones. In younger patients, sedation may be required to prevent excessive motion during the procedure. Moreover, it can be technically challenging to perform and intrathecal administration in very young patients, especially those with spinal column abnormalities (e.g. scoliosis).3 Clinicians may use ultrasound guidance or fluoroscopy to gain access to the thecal/subarachnoid space and to avoid injuring spinal cord or other nearby structures. 

If necessary, nusinersen can be administered into the cerebrospinal fluid in the cervical spine or intracisternally; however these approaches require specialist consultation (e.g. neurosurgery, interventional radiology, etc.)

The overlying skin should be cleaned in a two-step process; first with alcohol and second with skin disinfectant such as chlorhexidine or povidone-iodine.5 Note some institutions have prohibitions against or regulations endorsing a particular disinfectant. Regardless of disinfectant chosen, the area should be allowed to dry completely before continuing the procedure.5

With sterile gloves, the clinician should choose the L3/4 or L4/5 interspace and advance the spinal needle slowly into the subarachnoid space.3 A 21- to 25-gauge spinal anesthesia needle should be advanced in an “upward” fashion toward the umbilicus as this course runs parallel to the orientation of the spinous processes.3,6 Experienced practitioners may feel the moment when the spinal needle enters the subarachnoid space.6 In any case, the spinal needle is correctly positioned if cerebrospinal fluid is expressed.6

Per the manufacturer, 5 mL of cerebrospinal fluid should be removed prior to administering nusinersen—presumably to offset the 5 mL of solution that will be injected into the subarachnoid space.2 The oligonucleotide is administered as a bolus injection through the spinal anesthesia needle over 1 to 3 minutes.2 Once administration is complete, the needle is withdrawn and a small sterile dressing is placed on the site, since there is no need for a pressure dressing.5 In the clinical trial used to support the FDA application for nusinersen (Spinraza), patients were encouraged to lie flat for an hour after procedure. 3 

Of note, post-lumbar puncture syndrome has been observed after the administration of nusinersen (Spinraza).3 During the clinical trial, some patients experienced headache, back pain, and nausea associated with the injection.3 Patients and caregivers should be warned of this possible complication prior to the infusion. However, a new review on the efficacy and safety of nusinersen found that nusinersen was well tolerated across all studied age groups, and the reviewers deemed nusinersen both safe and effective for SMA patients.7


1. US Food and Drug Administration. FDA approves first drug for spinal muscular atrophy: New therapy addresses unmet medical need for rare disease. 2016; Accessed 10/26/2018.

2. SPINRAZA Prescribing Information. Cambridge, MA: Biogen.

3. Haché M, Swoboda KJ, Sethna N, et al. Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. Journal of Child Neurology. 2016;31(7):899-906.

4. Crooke ST, Baker BF, Witztum JL, et al. The Effects of 2′-O-Methoxyethyl Containing Antisense Oligonucleotides on Platelets in Human Clinical Trials. Nucleic Acid Ther. Jun 2017;27(3):121-129.

5. Doherty CM, Forbes RB. Diagnostic Lumbar Puncture. Ulster Med J. May 2014;83(2):93-102.

6. Babapour Mofrad R, Bouwman FH, Slot RER, et al. Lumbar puncture in patients with neurologic conditions. Alzheimers Dement (Amst). 2017;8:108-110.

7. Claborn MK, Stevens DL, Walker CK, et al. Nusinersen: A Treatment for Spinal Muscular Atrophy. Ann Pharmacother. Jul 1 2018:1060028018789956.